Renal tubular function in glycerol-induced acute renal failure.
The purpose of this study was to examine proximal and distal tubular function in rats with nonoliguric, myohemoglobinuric acute renal failure (ARF). ARF was induced with glycerol (50%, 10 ml/kg of body wt, i.m.), and renal function was studied 24 hours after glycerol or saline (controls) injection. Glycerol injection caused a 50 to 90% depression in GFR and a significant rise in blood urea nitrogen concentration. Animals with ARF exhibited glycosuria with normal blood sugar levels and a striking depression in tubular glucose reabsorption per milliliter of GFR. The capacity to reabsorb (mEq/liter GFR) was intact at normal blood bicarbonate levels, but was markedly depressed when blood bicarbonate was raised. The tubular maximum for para-aminohippurate (PAH) secretion and the renal extraction fraction of PAH were strikingly depressed in rats with ARF. Distal acidification as assessed by the urine-to-blood gradient of PCO2 (UB PCO2) was normal both during maximal alkalinization of the urine with bicarbonate (urine pH, approximately 7.8) or during neural phosphate infusion (urine pH, approximately 7.0). Net acid excretion per milliliter GFR and minimal urine pH (less than 5.5) following 3 days of ammonium chloride ingestion was similar in control and ARF animals. Potassium excretion was intact in maximal urinary osmolality were significantly altered in animals with ARF. Cortical and outer medullary Na-K-ATPase specific activities were significantly depressed in ARF rats. This occurred as a consequence of enzyme loss and not secondary to alterations in enzyme kinetics of absolute tubular sodium reabsorption. Light and electron microscopy showed diffuse proximal tubular damage, whereas glomeruli and distal tubules were intact. These data demonstrate that glycerol injection produces a diffuse proximal tubular transport defect associated with histologic and enzymatic alterations.
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005990:Glycerol; D007671:Kidney Concentrating Ability; D007684:Kidney Tubules / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010710:Phosphates / Q000494:pharmacology / Q000652:urine; D011188:Potassium / Q000652:urine; D051381:Rats; D014867:Water / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D001639:Bicarbonates; D010710:Phosphates; D014867:Water; D002245:Carbon Dioxide; D005947:Glucose; D005990:Glycerol; D011188:Potassium; D010130:p-Aminohippuric Acid